Comparison of the clinical characteristics of benign and malignant eyelid lesions: an analysis of 1423 eyelid lesions, compared between ophthalmology department and plastics department.

PURPOSE: Oculoplastic surgeons excise and reconstruct eyelid tumors, although plastic surgeons have traditionally managed these cases. Current demand of this surgery is growing, and planning referral services is a health management necessity. This pilot study retrospectively reviewed same population eyelid specimens excised by both disciplines comparing data. METHODS: Clinical and epidemiologic features of 1423 eyelid lesions biopsied between 2015- 2020 in Emek Medical Center (EMC), Israel were reviewed. RESULTS: Among 1423 specimens, 1210 (85.0%) were benign and 213 (15.0%) were malignant/pre-malignant. Mean age at diagnosis was significantly higher in malignant tumors than in benign tumors (76 and 59 years respectively, p value < 0.001). The most common benign eyelid lesions were soft fibroma (20.1%), seborrheic keratosis (11.0%) and melanocytic nevus (10.3%). The most common malignant/pre-malignant eyelid tumors were basal cell carcinoma (BCC) (9.2%), actinic keratosis (2.6%) and Bowen's disease (1.9%). Ophthalmology removed 37 malignant/pre-malignant lesions (5.4%) out of 683 compared to plastics removing 142 malignant/pre-malignant lesions out of 740 (19.2%) specimens. Eyelid malignancy in the plastics department was significantly higher than in the ophthalmology department (p value < 0.001). 270 (70.0%) lesions caused by UV exposure were removed by plastics and 116 (30.0%) were removed by ophthalmology (p value < 0.001). CONCLUSIONS: Eyelid lesions in patients aged 76 or older are more likely to be malignant. Ophthalmology eyelid specimens in younger patients are more commonly benign and related to inflammation. Specimens from the plastics department are more commonly malignant, related to UV-exposure, and are from older patients. This difference may be due to a misconception that plastic surgeons have more eyelid cancer reconstruction experience than oculoplastic surgeons, or less awareness of the oculoplastic expertise available today.

Adult Henoch-Schönlein Purpura: Comprehensive Assessment of Demographic, Clinical, and Histopathological Features as Predictors for Systemic Involvement.

BACKGROUND: Henoch-Schönlein purpura (HSP) is a small-vessel IgA-predominant vasculitis. A major challenge in managing adult HSP is the difficulty assessing the risk of systemic involvement. There is currently a paucity of data in this area. OBJECTIVE: The objective of this study was to determine demographic, clinical, and histopathological features associated with systemic involvement in adult HSP. METHODS: In this retrospective study, we reviewed demographical features and clinical and pathology data of 112 adult HSP patients seen at Emek Medical Center between January 2008 and December 2020. RESULTS: Of these patients, 41 (36.6%) had renal involvement, 24 (21.4%) had gastrointestinal tract involvement, and 31 (27.7%) had joint involvement. Age >30 years (p = 0.006) at diagnosis was an independent predictor of renal involvement. Platelet count (<150 K/µL) (p = 0.020) and apoptosis of keratinocytes on skin biopsy (p = 0.031) were also associated with renal involvement. History of autoimmune disease (p = 0.001), positive c-antineutrophil cytoplasmic antibody (p = 0.018), positive rheumatoid factor (p = 0.029), and elevated erythrocyte sedimentation rate (p = 0.04) were associated with joint involvement. Female sex (p = 0.003), Arab race (p = 0.036), and positive pANCA (p = 0.011) were associated with gastrointestinal tract involvement. LIMITATIONS: This study is retrospective. CONCLUSION: These findings may serve as a guide to stratify risk in adult HSP patients so that those at higher risk can be monitored more closely.

Risk of Melanoma in Patients with Basal Cell Carcinoma: A Population-based Cohort Study.

Basal cell carcinoma is the most prevalent cancer in Caucasians worldwide. The aim of this study was to examine the overall risk of melanoma among patients diagnosed with basal cell carcinoma. This population-based retrospective cohort study included data from January 2010 to December 2018 from the databases of the Clalit Health Maintenance Organization and 2 major pathology laboratories in North District, Israel. The incidence and hazard ratio of melanoma in patients with a diagnosis of basal cell carcinoma were determined. Of 466,700 participants, 51% were women and the mean (standard deviation) follow-up was 6.7 (2.9; range 1-9) years. A total of 3,338 patients were diagnosed with basal cell carcinoma during the study period, 82 of whom subsequently developed melanoma. Patients with basal cell carcinoma had a significantly higher incidence of melanoma than patients without basal cell carcinoma (2.46% vs 0.37%; p < 0.0001). Univariate Cox regression analysis revealed a hazard ratio of 6.6 (95% confidence interval: 3.6-12.1; p < 0.0001) for melanoma in patients with a diagnosis of basal cell carcinoma. In conclusion, a diagnosis of basal cell carcinoma confers a significant risk of melanoma.

Potential di-genic contribution to guttate leukoderma as the predominant feature of epidermolysis bullosa simplex.

Inherited epidermolysis bullosa (EB) simplex is a heterogeneous group of skin fragility disorders caused by mutations in genes encoding cell-cell or cell-matrix adhesion proteins. A recently identified, rare subtype of EB simplex is due to bi-allelic mutations in the EXPH5 gene, which encodes exophilin5, an effector protein of the Rab27B GTPase involved in intracellular vesicle trafficking and exosome secretion. The EXPH5 EB subtype is characterized by early-onset skin blisters and scars, mainly on extremities, and varying degrees of pigmentary alterations. Here, we present a 31-year-old female with diffuse guttate hypopigmentation on the trunk and extremities since early childhood, with no apparent blisters or scars. We employed whole exome sequencing of germline DNA extracted from the patient's leukocytes to determine the genetic aetiology of the phenotype. A novel homozygous variant in EXPH5, c.1153C>T causing a premature stop codon at amino acid Glutamine 385, was identified. Histologic examination after skin pricking disclosed focal keratinocyte detachment typical to EB. Additionally, we identified a deleterious-predicted variant in ENPP1, a gene associated with disturbed transfer of melanosomes to keratinocytes in Cole disease. Our report expands the clinical spectrum of inherited EB simplex with a possible di-genic synergism contributing to co-presentation with guttate leukoderma.

Tissue microarrey: a potential cost-effective approach for mismatch repair testing in colorectal cancer.

BACKGROUND: Deficiencies in Mismatch Repair (MMR) proteins are one of the major pathways in the development of colorectal cancer (CRC). MMR status evaluation is recommended in every new CRC patient. However, this is not fully implemented due to high costs. Tissue microarray (TMA) enables allocating tissue cores from few specimens to a single paraffin block. The primary objective of this study was to evaluate the accuracy of TMA MMR immunohistochemistry (IHC) compared to whole slide. The secondary objective was to evaluate and validate automatic digital image analysis software in differentiating pathological and normal TMA cores. METHODS: Pathological cores were defined if at least one MMR protein was unstained. Tumoral and normal tissue of 11 CRC patients with known MMR status was used to obtain 623 TMA cores. The MMR staining of each core was evaluated by a pathologist and compared to the whole slide result. Digital analysis software by 3DHistech Ltd. was used to identify cell nucleus and quantify nuclear staining in 323 tissue cores. To identifying pathological tissue, cores the cohort was divided into a test (N = 146 cores) and validation sets (N = 177 cores). A staining intensity score (SIS) was developed, and its performance compared to the pathologist review of each core and to the whole slide result. RESULTS: Compared to the whole slide, the pathologist's assessment had 100% sensitivity (n/N = 112/112) and 100% specificity (n/N = 278/278) with 95% lower limit of 97 and 99% respectively. The area under the receiver operating characteristic (ROC) curve of SIS was 77%. A cutoff of 55 was obtained from the ROC curve. By implementing the cutoff in the validation dataset, the SIS had sensitivity and specificity of 98.2% [90.1-100%] and 58.5% [49.3-67.4%] respectively. CONCLUSIONS: The MMR status of CRC can be evaluated in TMA tissue cores thus potentially reducing MMR testing costs. The SIS can be used as triage indicator during pathologic review. TRIAL REGISTRATION: Institutional ethical approval was granted for the performance of this study (Emek Medical Center Ethics ID: EMC-19-0179).

Role of oncogenic viruses in the development ocular surface squamous neoplasia.

PURPOSE: The pathogenesis of ocular surface squamous neoplasia is not fully understood. Therefore, we evaluated the role of oncogenic viruses in the pathogenesis of ocular surface squamous neoplasia in Israel. METHODS: Patients with ocular surface squamous neoplasia were enrolled in this retrospective study. The specimens were taken during 2004-2015 from two big centers: Emek Medical Center, Afula and the Hadassah Medical Center, Jerusalem. All the specimens (totally 26) were analyzed by immunohistochemistry for evidence of oncogenic viruses that included Human Papilloma virus, Herpes Simplex virus and Cytomegalovirus infection and 14 samples were examined by polymerase chain reaction. In addition, all the samples were examined for Epstein Barr virus infection by immunohistochemistry and Epstein Barr encoding region test. RESULTS: Twenty-six patients were included with a mean age of 61.81 [Formula: see text] 3.83 years (mean [Formula: see text]. Immunohistochemistry staining and Epstein Barr encoding region test did not detect any of the oncogenic viruses in the 26 samples. Human Papilloma virus-16 and -18, and Herpes Simplex virus were detected by polymerase chain reaction in 14.2%, 7% and 7%, respectively. CONCLUSION: We conclude from our study that oncogenic viruses may play a role in the pathogenesis of ocular surface squamous neoplasia in Israel.

Loss of EIF4G2 mediates aggressiveness in distinct human endometrial cancer subpopulations with poor survival outcome in patients.

The non-canonical translation initiation factor EIF4G2 plays essential roles in cellular stress responses via translation of selective mRNA cohorts. Currently there is limited and conflicting information regarding its involvement in cancer development and progression. Here we assessed its role in endometrial cancer (EC), in a cohort of 280 EC patients across different types, grades, and stages, and found that low EIF4G2 expression highly correlated with poor overall- and recurrence-free survival in Grade 2 EC patients, monitored over a period of up to 12 years. To establish a causative connection between low EIF4G2 expression and cancer progression, we stably knocked-down EIF4G2 in two human EC cell lines in parallel. EIF4G2 depletion resulted in increased resistance to conventional therapies and increased the prevalence of molecular markers for aggressive cell subsets, altering their transcriptional and proteomic landscapes. Prominent among the proteins with decreased abundance were Kinesin-1 motor proteins, KIF5B and KLC1, 2, 3. Multiplexed imaging of the EC patient tumor cohort showed a correlation between decreased expression of the kinesin proteins, and poor survival in patients with tumors of certain grades and stages. These findings reveal potential novel biomarkers for Grade 2 EC with ramifications for patient stratification and therapeutic interventions.

Complete digital pathology transition: A large multi-center experience.

INTRODUCTION: Transitioning from glass slide pathology to digital pathology for primary diagnostics requires an appropriate laboratory information system, an image management system, and slide scanners; it also reinforces the need for sophisticated pathology informatics including synoptic reporting. Previous reports have discussed the transition itself and relevant considerations for it, but not the selection criteria and considerations for the infrastructure. OBJECTIVE: To describe the process used to evaluate slide scanners, image management systems, and synoptic reporting systems for a large multisite institution. METHODS: Six network hospitals evaluated six slide scanners, three image management systems, and three synoptic reporting systems. Scanners were evaluated based on the quality of image, speed, ease of operation, and special capabilities (including z-stacking, fluorescence and others). Image management and synoptic reporting systems were evaluated for their ease of use and capacity. RESULTS: Among the scanners evaluated, the Leica GT450 produced the highest quality images, while the 3DHistech Pannoramic provided fluorescence and superior z-stacking. The newest generation of scanners, released relatively recently, performed better than slightly older scanners from major manufacturers Although the Olympus VS200 was not fully vetted due to not meeting all inclusion criteria, it is discussed herein due to its exceptional versatility. For Image Management Software, the authors believe that Sectra is, at the time of writing the best developed option, but this could change in the very near future as other systems improve their capabilities. All synoptic reporting systems performed impressively. CONCLUSIONS: Specifics regarding quality and abilities of different components will change rapidly with time, but large pathology practices considering such a transition should be aware of the issues discussed and evaluate the most current generation to arrive at appropriate conclusions.

Molluscum contagiosum presenting as periorbital abscess in immunocompetent children.

Molluscum contagiosum presenting as a periorbital region abscess is unusual. The virus generally causes a self-limiting localized disease in children. Presentation as an abscess has been reported mainly in immunocompromised patients. We performed a retrospective study of ten children treated for Molluscum contagiosum infection presenting as periorbital abscess. Data investigated included age, immunocompetence, systemic antibiotic treatment, clinical findings, and histopathology. All children were immunocompetent. Bacterial cultures taken in six of the ten children were positive in two. Seven patients received oral antibiotics before presentation but required IV antibiotics on admission. One patient received IV antibiotics only. All antibiotic treatment had very limited effect. Two patients had no antibiotic treatment. CT imaging in one case where orbital cellulitis was suspected showed no significant intraorbital findings with anterior involvement only. Nine out of ten children had surgery and intra-operative cryotherapy at our center with immediate improvement and recovery. One child whose parents initially refused surgical excision had initial limited clinical improvement of periorbital swelling with antibiotics. However, the lesions were excised shortly following discharge from our hospital at another medical center with a complete cure. Molluscum is a cause of periorbital abscess in immunocompetent children which should be part of the differential diagnosis in periorbital/adnexal infection. Antibiotic treatment has a limited effect, and the abscess is most likely a virally triggered reaction. Surgical excision and intra-operative cryotherapy are curative of the disease in our experience.

Is Demodex Blepharitis Connected With Cataract Surgery?

PURPOSE: To determine whether there is an increased incidence of Demodex of the eyelashes among patients after cataract extraction surgery. DESIGN: Prospective, noncomparative clinical study. METHODS: A cohort of patients who underwent cataract extraction surgery had several eyelashes removed preoperatively that were examined independently by the hospital laboratory for the presence of the Demodex mite. This was repeated 3 weeks after surgery. During several postoperative weeks, patients received the standard treatment of steroid drops alone for a period as individually required. RESULTS: A total of 62 patients were included in the study (31 men and 31 women), with a mean age of 71.04 years (range, 47-87). In the group positive for Demodex, the male-to-female ratio was 2:3 (P = .2772). Demodex colonization was observed in 22.58% of samples before cataract surgery and in 32.26% after cataract surgery and topical postoperative steroid therapy (P = .0143). CONCLUSIONS: There is a statistically significant increase in Demodex colonization of eyelashes after cataract surgery and postoperative topical steroid treatment. Although Demodex colonization does not necessarily cause blepharitis, our findings of increased colonization should raise the possibility of Demodex blepharitis being considered by ophthalmologists in patients with chronic postoperative eye discomfort after cataract surgery. This study was carried out at the Emek Medical Center.

Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay.

Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors of the biopsied lesions. SCC invasiveness is also predicted by histomorphological factors, such as the degree of differentiation or the mitotic index, while BCCs are typically considered non-invasive. The above subjective measures do not provide direct, objective prognosis of cellular invasiveness in each specific sample. Hence, we have developed a mechanobiology-based approach to rapidly determine sample invasiveness. Here, cells from 15 fresh tissue samples of suspected non-melanoma skin cancer were seeded on physiological-stiffness (2.4 kPa) synthetic gels, and within 1-h invasive cell subsets were observed to push/indent the gel surface; clinicopathological results were separately obtained using standard protocols. The percentage of indenting cells from invasive (26.2 ± 2.4%) and non-invasive (4.8 ± 0.5%) SCC samples differed significantly (p < 0.0001), with well-separated invasiveness cutoffs of, respectively, > 12% and < 5%. The mechanical invasiveness directly agrees with the SCC cell-differentiation state, where over 3.3-fold more (p < 0.0001) cells from moderately differentiated samples indent the gels as compared to well-differentiated cell samples. In BCCs, < 20% of cells typically indented, and a highly migratory, desmoplastic sample was identified with 46%. By providing rapid, quantitative, early prognosis of invasiveness and potential metastatic risk, our rapid technology may facilitate informed (bed-side) decision making and choice of disease-management protocols on the time-scale of the initial diagnosis and surgical excision.

The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.

An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. Cultured keratinocytes and organotypic skin equivalents depleted of Dsg1 exhibited reduced Cx43 expression, rescued upon re-introduction of wild-type Dsg1, but not Dsg1 constructs modeling SAM syndrome-causing mutations. Ectopic Dsg1 expression increased cell-cell dye transfer, which Cx43 silencing inhibited, suggesting that Dsg1 promotes GJ function through Cx43. As GJA1 gene expression was not decreased upon Dsg1 loss, we hypothesized that Cx43 reduction was due to enhanced protein degradation. Supporting this, PKC-dependent Cx43 S368 phosphorylation, which signals Cx43 turnover, increased after Dsg1 depletion, while lysosomal inhibition restored Cx43 levels. These data reveal a role for Dsg1 in regulating epidermal Cx43 turnover.

Unusual presentation of epidermoid cyst mimicking breast cancer involving the areola-Case report.

INTRODUCTION: Epidermoid cyst is very common benign lesion of the skin. And may appear anywhere on the surface of the body. Diagnosis is made in most cases by clinical examination, but histological evaluation may be needed in unusual cases. PRESENTATION OF CASE: We report a rare case of a 44 year-old woman who presented with a rapidly growing inflamed mass localized to the left areola, which grew to 4 cm in diameter within a few months. The diagnosis of malignancy was ruled out following pathology examination consistent with epidermoid cyst. After a course of antibiotics, she underwent surgery with nipple sparing and reconstruction of the areola. DISCUSSION: Preoperative diagnosis based on biopsy enable limited surgical excision and preservation of the nipple. Reconstruction of the areola by local areolar flap enable good aesthetic result. CONCLUSION: It is important to be aware of this entity of epidermoid cyst mimicking breast cancer, and the treatment options available in these cases.

Intralesional cryosurgery for the treatment of basal cell carcinoma of the lower extremities in elderly subjects: a feasibility study.

BACKGROUND: Incidences of basal cell carcinoma (BCC) on the lower extremities in elderly patients are rising. Surgical approaches to the treatment of BCC are subject to possible difficulties in healing, failure of skin grafts, and wound infection. This study assessed the efficacy of intralesional cryosurgery in the treatment of BCC of the lower limbs in elderly patients. METHODS: This study included eight patients aged >60 years in whom a total of 10 nodular or superficial BCCs of the lower limbs were confirmed by biopsy. The patients' medical histories revealed comorbidities including hypertension, diabetes, hypercholesterolemia, venous insufficiency, and deep vein thrombosis of the legs, congestive heart failure, chronic renal failure, and ischemic heart disease. Using liquid nitrogen, an intralesional cryosurgery needle (CryoShape) was inserted into the tumor to facilitate its complete freezing. Treatment success was confirmed by biopsy taken approximately 3 months after complete healing of the cryo-wound. RESULTS: The average size of the lesions treated was 2.49 cm(2) (16.4 × 15.2 mm). Mean recovery time was 79.9 days. Biopsies were obtained at a mean of 85.3 days after the wound had healed. All 10 biopsies verified the complete destruction of the tumor. There was no evidence of wound infection or tumor recurrence over a follow-up period of 28 months. CONCLUSIONS: This study demonstrates that a single intralesional cryosurgery session can completely eradicate BCC on the lower extremities in elderly patients. This technique is associated with relatively minor complications, is well tolerated, and represents a safe and effective therapeutic modality for BCC of the lower limbs.

[Role of osteopontin in the formation of microcalcifications in breast cancer]. / Az osteopontin szerepe a microcalcificatiók kialakulásában emlócarcinomákban.

INTRODUCTION: Osteopontin, a non-collagen, Ca-binding phosphoprotein, plays roles in both physiological and pathological mineralisation processes. Its expression may be severely altered in malignant tumours. AIM: To investigate the presence of this protein in breast tumours showing mammographic microcalcifications. MATERIAL: In this study the authors investigated immunohistochemically the osteopontin expression in 26 breast tumours. The elemental composition of the microcalcifications of the same tumours was also examined with energy dispersive spectrometer linked to a scanning electron microscope. RESULTS: Osteopontin expression was found within the tumours in the tumour cells, in vascular smooth muscle cells, in the myoepithelial cells of the normal ducts, and in macrophages. Extracellular osteopontin positivity was seen around calcified foci. There was no correlation between osteopontin positivity and the examined prognostic factors: grade, type and size of the tumour, axillary lymph nodes status, or age. Two types of microcalcifications were seen: 1. Ca-phosphate only, 2. Those composed of various other elements. CONCLUSION: The presence of osteopontin in the vicinity of calcified foci and in the vessel walls seems to support the hypothesis that osteopontin takes part in calcification process.